Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation
Damberger, Fred F.
Allain, Frédéric H.-T.
Schertler, Gebhard F.X.
Sommer, Martha E.
Veprintsev, Dmitry B.
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
Cellular functions of arrestins are determined in part by the pattern of phosphorylation on the G protein-coupled receptors (GPCRs) to which arrestins bind. Despite high-resolution structural data of arrestins bound to phosphorylated receptor C-termini, the functional role of each phosphorylation site remains obscure. Here, we employ a library of synthetic phosphopeptide analogues of the GPCR rhodopsin C-terminus and determine the ability of these peptides to bind and activate arrestins using a variety of biochemical and biophysical methods. We further characterize how these peptides modulate the conformation of arrestin-1 by nuclear magnetic resonance (NMR). Our results indicate different functional classes of phosphorylation sites: ‘key sites’ required for arrestin binding and activation, an ‘inhibitory site’ that abrogates arrestin binding, and ‘modulator sites’ that influence the global conformation of arrestin. These functional motifs allow a better understanding of how different GPCR phosphorylation patterns might control how arrestin functions in the cell. Show more
Journal / seriesNature Communications
Pages / Article No.
PublisherNature Publishing Group
MoreShow all metadata